Neuroplasticity, the brain's capacity to reorganise its structure and function, is a transdiagnostic feature across psychiatric and neurodegenerative diseases and a putative mechanism of action for pharmacological interventions. [11C]-UCBJ positron emission tomography (PET), which quantifies synaptic vesicle glycoprotein 2A (SV2A) density, offers the most direct in vivo measure of human...
Background: Epidemiological data on psychedelic use in Italy is limited. In this study, Italian responders in the Global Psychedelic Survey 2025 were subanalyzed to describe patterns of use, motivations, subjective experiences, and health correlates. Methods: Adults (≥21 years) with lifetime psychedelic exposure, residing in or born in Italy or San Marino, were surveyed in a web-based,...
We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and...
BACKGROUND: Alcohol use disorder and treatment-resistant depression (TRD) often co-occur, presenting a major clinical challenge with limited effective treatments. However, ketamine produces rapid antidepressant effects and has shown promise in reducing alcohol use, and acceptance and commitment therapy (ACT) can be effective for both substance use and mood disorders. This study explores the...
Under the influence of psychedelics, people often report encountering "entities" who seem to have their own autonomous agency. Depending on the cultural milieu, these entities are reported to take a variety of forms, including spirits, elves, ancestors, or fragments of the self. Encounters with such beings hold a central place in many traditions of psychedelic practice around the world. And...
Humphry Osmond coined the term ‘psychedelic’ in 1956, conjoining ‘psyche’ for ‘soul’ and ‘delic’ from ‘dêlos’ for ‘to manifest’ or ‘illuminate.’ Soul-illumination is an adjective that describes a psychological state or process. However, Osmond’s intention was to use the adjective to name— not just a state— but a category of drug that can induce the subjective effect as its principal action;...
It is 60 years since ketamine was first tested in humans as an alternative but safer anaesthetic to PCP (phencyclidine) (Corssen and Domino 1966). It became widely used as the “buddy drug” for combatants in the Vietnam War: because of its great safety margin, it could be injected into wounded personnel by their buddies to relieve pain before the arrival of the medical team. Because of...
Background Ketamine exerts potent but transient antidepressant effects in treatment-resistant depression (TRD). Combinations of ketamine and psychotherapy have attracted interest, but no trial has investigated a psychedelic model of ketamine–psychotherapy for TRD to our knowledge. Aims This secondary analysis of a randomised clinical trial (RCT) explores the therapeutic effects and experiential...
Psychedelic substances exhibit complex interactions with the 'set and setting' of use, that is, the mental state of the user and the environment in which a psychedelic experience takes place. Despite these contextual variables' known importance, psychedelic research has lacked methodological rigor in reporting extra-pharmacological factors. This study aimed to generate consensus-based...
Abstract Music is integral to Psilocybin-assisted psychotherapy (PAP), believed to enhance therapeutic outcomes by structuring experiences and facilitating emotional expression. However, the effects of conducting PAP without music are underexplored. This study examines the experiences of two breast cancer patients undergoing psilocybin therapy under Canada's compassionate access program,...
Since its synthesis in 1962, ketamine has been widely used in diverse medical contexts, from anesthesia to treatment-resistant depression. However, interpretations of ketamine's subjective effects remain polarized. Biomedical frameworks typically construe the drug's experiential effects as dissociative or psychotomimetic, while psychedelic paradigms emphasize the potential therapeutic merits of...
Background: The resurgent interest in psychedelic-assisted therapy for conditions like depression, end-of-life anxiety, and post-traumatic stress disorder is generating highly promising results. Within this therapeutic context, music's role is multifaceted, seen as a critical environmental component and even akin to a hidden therapist. Contemporary clinical protocols often advocate for music...
Abstract Background Psychedelic substances exhibit complex interactions with the ‘set and setting’ of use, i.e., the internal state of the user and the external environment in which a psychedelic experience takes place. Despite the known importance of these contextual variables, psychedelic research has suffered from methodological weaknesses in reporting extra-pharmacological factors and from...
Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving...
Background: Reference to an intrinsic healing mechanism or an ‘inner healer’ is commonplace amongst psychedelic drug-using cultures. The ‘inner healer’ refers to the belief that psychedelic compounds, plants or concoctions have an intrinsically regenerative action on the mind and brain, analogous to intrinsic healing mechanisms within the physical body, for example, after sickness or injury....
Currently, individuals with personal or familial histories of psychopathological experiences of psychosis, psychotic spectrum disorders, bipolar disorder, and similar conditions are excluded from most psychedelic clinical trials, studies, and treatment programs. This study sought to determine why such an exclusion exists, what the implications of the exclusion criteria are, and if there was...
We present the first evidence that sub-anesthetic ketamine infusions for treatment resistant depression (TRD) may facilitate deprescription of long-term benzodiazepine/z-drugs (BZDRs). Long-term BZDR prescriptions are potentially harmful yet common, partly because of challenging withdrawal symptoms. Few pharmacological interventions have evidence for facilitating BZDR discontinuation, and none...
Background Subanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine’s mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy,...
Novel and traditional psychedelic medicines are attracting interest as potential treatments of mental illness. Before psychedelic therapies can be made available in culturally safe and effective ways to diverse peoples, the field must grapple with the complex legacies of colonialism and ongoing clashes between biomedical and Indigenous Ways of Knowing. This article presents results of a pilot...
Medical Aid in Dying (MAiD) is the act of a healthcare provider ending a patient's life, at their request, due to unbearable suffering from a grievous and incurable disease. Access to MAiD has expanded in the last decade and, more recently, it has been made available for psychiatric illnesses in a few countries. Recent studies have found that such psychiatric requests are rapidly increasing and...
Background Psychedelic drug experiences are shaped by current-moment contextual factors, commonly categorized as internal (set) and external (setting). Potential influences of past environments, however, have received little attention. Aims To investigate how previous environmental stimuli shaped the experiences of patients receiving ketamine for treatment-resistant depression (TRD), and...
Psychedelics have been already used by human societies for more than 3000 years, mostly in religious and healing context. The renewed interest in the potential application of psychedelic compounds as novel therapeutics has led to promising preliminary evidence of clinical benefit in some psychiatric disorders. Despite these promising results, the potential for large-scale clinical application...
BACKGROUND: Alcohol use disorder is highly prevalent and has important economical, societal, psychiatric, and medical consequences. All currently approved therapeutic approaches targeting alcohol dependence have relatively modest effects and high relapse rates. Recent evidence suggests that ketamine may be an effective intervention to treat alcohol use disorder and alcoholic withdrawal. This...
Objective Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. Methods A systematic...